This proposal requests renewal of the NIEHS Center Grant "Trace Contaminants as Environmental Health Hazards of Humans" for a five-year funding period, 1995-2000. Now, in its 20th year, this grant has provided the continuity that has been crucial to developing and maintaining a national resource in environmental toxicology. The Center has never attempted to cover every area of toxicology, but provides support for the Research Cores in selected areas of toxicology: Neurobehavioral toxicology, Pulmonary toxicology and Cellular & Molecular toxicology. Common interests nurture the growth of our Center as a whole and expand the knowledge base for defining mechanisms of action. For example, receptor-mediated actions of toxicants such as dioxin, estrogenic xenobiotics and lead, or the processes involved in cellular defense mechanisms such as antioxidant systems, biotransformation and metal complexation with sulfur ligands bring together novel perspectives. An exciting theme emerging from these common interests is that many toxicants act by causing dysregulation of normal homeostatic cellular processes. We view this concept as unique and significant in guiding our approaches for defining mechanisms of action. Three Research Clusters represent interactions among faculty within the Center: Toxic Metals, Space Environmental Health, and the 'Sulfur Society' include researchers from across the core groups, and attract collaborators from around the country and the world. The Research Cores receive scientific, technical and administrative support from five Shared Facilities: the analytical facility, biostatistics, pathology/morphology, including a new transgenic laboratory, and two new facilities, the micro-sampling and molecular/cellular biology. Also, several important Center Resources, belonging to individual faculty, are available on a collaborative basis. Pilot Projects stimulate new ideas and garner preliminary data for grant applications. An Enrichment Program assists in funding visiting scientist and seminars, extramural faculty development and the Rochester International Conferences in Environmental Toxicity. The Center contributes to and derives further enrichment from a well-established Ph.D. training program supported by an NIEHS training grant. The Center is developing cooperative working relationships with a new Occupational Health Division, housed in the same department as the Center. A new Outreach Program has been started to ensure that scientific knowledge and other benefits from our research are made available directly to citizens at the local, state and federal levels.